The overall aim of this K24 Mid-Career Investigator Award in Patient-Oriented Research is to allow Dr. Frances Levin to continue to expand her programmatic line of clinical research and mentoring. Two main objectives drive the investigator's work: 1) develop pharmacotherapies that consider the heterogeneity of substance abusers and 2) provide mentorship to junior clinical investigators. Although there has been intensive investigation of medications and vaccines to treatment cocaine dependence, effective treatments remain elusive. Substance abuse is often accompanied with additional psychiatric comorbidity yet empirically-based treatments are limited. Moreover, there has been minimal research evaluating pharmacotherapies for cannabis use disorders, despite its substantial morbidity. Primary activities for this competing renewal and prior K24-funded accomplishments include developing novel combined medication treatment strategies for cocaine and cannabis-dependent individuals, testing new innovative behavioral interventions combined with pharmacotherapies for cocaine and other addictive disorders, and ensuring that promising human laboratory findings are efficiently tested in the outpatient treatment setting. During the course of this competing renewal K24 award Dr. Levin will be Principal Investigator of a U54 (a converted P50), a multi-site U1 (a converted R01), an R01, and Principal Investigator of a T32 that targets the training of physicians. Additionally, she will serve as a co-investigator or co-investigator on several other RO1s/R21s with both junior and mid-career colleagues that extend her areas of interest. And she will serve as a mentor on several mentored K awards. The career development plan for this application will expand Dr. Levin's knowledge into the areas of technology-based treatments, neuroimaging techniques, and stress-induced paradigms to predict treatment response through synergistic collaborations with other investigators. The mentoring plan incorporates trainees at various levels of development: 1) pre- doctoral trainees (medical students); 2) postdoctoral trainees (psychiatric residents and fellows); and 3) junior faculty. An overarching career goal has been to mentor clinical investigators and advance knowledge in the substance abuse field through reciprocal collaborations with other investigators, often with individuals that Dr. Levin has mentored or is currently mentoring. Of great public concern is a dearth of adequately trained physician investigators interested in clinical substance abuse research careers. Through Dr. Levin's activities it is hoped that the treatment of substance abusers will improve, both through her research and collaborations with colleagues, and through her training of the next generation of clinical investigators.